345 research outputs found
Integral representation of the linear Boltzmann operator for granular gas dynamics with applications
We investigate the properties of the collision operator associated to the
linear Boltzmann equation for dissipative hard-spheres arising in granular gas
dynamics. We establish that, as in the case of non-dissipative interactions,
the gain collision operator is an integral operator whose kernel is made
explicit. One deduces from this result a complete picture of the spectrum of
the collision operator in an Hilbert space setting, generalizing results from
T. Carleman to granular gases. In the same way, we obtain from this integral
representation of the gain operator that the semigroup in L^1(\R \times \R,\d
\x \otimes \d\v) associated to the linear Boltzmann equation for dissipative
hard spheres is honest generalizing known results from the first author.Comment: 19 pages, to appear in Journal of Statistical Physic
Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.
Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8-fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role
Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models
<p>Abstract</p> <p>Background</p> <p>Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood.</p> <p>Methods</p> <p>The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS).</p> <p>The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses.</p> <p>The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer.</p> <p>Results</p> <p>In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (<it>CHKA</it>, <it>CHKB</it>) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (<it>PLA2G4A</it>) and phospholipase B1 (<it>PLB1</it>) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer.</p> <p>Conclusions</p> <p>The differences in choline metabolite concentrations corresponded well with differences in gene expression, demonstrating distinct metabolic profiles in the xenograft models representing basal-like and luminal-like breast cancer. The same characteristics of choline metabolite profiles were also observed in patient material from ER+/PgR+ and triple-negative breast cancer, suggesting that the xenografts are relevant model systems for studies of choline metabolism in luminal-like and basal-like breast cancer.</p
Studies on sulfatides by quadrupole ion-trap mass spectrometry with electrospray ionization: Structural characterization and the fragmentation processes that include an unusual internal galactose residue loss and the classical charge-remote fragmentation
Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer
Introduction
Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach.
Methods
Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39).
Results
Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1).
Conclusions
These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response
First Measurement of the Tensor Structure Function of the Deuteron
The \Hermes experiment has investigated the tensor spin structure of the
deuteron using the 27.6 GeV/c positron beam of \Hera. The use of a tensor
polarized deuteron gas target with only a negligible residual vector
polarization enabled the first measurement of the tensor asymmetry \At and
the tensor structure function \bd for average values of the Bj{\o}rken
variable and of the squared four-momentum transfer . The quantities \At and \bd are found to be
non-zero. The rise of \bd for decreasing values of can be interpreted to
originate from the same mechanism that leads to nuclear shadowing in
unpolarized scattering
Double hadron leptoproduction in the nuclear medium
First measurement of double-hadron production in deep-inelastic scattering
has been measured with the HERMES spectrometer at HERA using a 27.6 GeV
positron beam with deuterium, nitrogen, krypton and xenon targets. The
influence of the nuclear medium on the ratio of double-hadron to single-hadron
yields has been investigated. Nuclear effects are clearly observed but with
substantially smaller magnitude and reduced -dependence compared to
previously measured single-hadron multiplicity ratios. The data are in fair
agreement with models based on partonic or pre-hadronic energy loss, while they
seem to rule out a pure absorptive treatment of the final state interactions.
Thus, the double-hadron ratio provides an additional tool for studying
modifications of hadronization in nuclear matter
Nuclear Polarization of Molecular Hydrogen Recombined on a Non-metallic Surface
The nuclear polarization of molecules formed by recombination
of nuclear polarized H atoms on the surface of a storage cell initially coated
with a silicon-based polymer has been measured by using the longitudinal
double-spin asymmetry in deep-inelastic positron-proton scattering. The
molecules are found to have a substantial nuclear polarization, which is
evidence that initially polarized atoms retain their nuclear polarization when
absorbed on this type of surfac
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